Cancer treatment often involves surgery, radiation therapy and chemotherapy, in varying combinations. However, these treatments all too frequently are just temporary solutions to a progressively life-threatening disease. Cancer cells can escape surgical intervention, be unresponsive to radiation or develop resistance to chemotherapeutic agents. In addition, these treatments typically have significant adverse physiological side effects. Research is currently underway to develop methods for stimulating a patient's own immune system, but development of such methods is still in its infancy.
In the recent years, antibody-based therapy has become more frequently used for an increasing number of human cancers. There are more than 20 monoclonal antibody drugs treatments in use today for a variety of malignancies, including trastuzumab (Herceptin) for breast cancer, rituximab (Rituxan) for lymphoma, and cetuximab (Erbitux) for head and neck squamous cell carcinoma. However, the clinical efficacy of such antibody treatments has been highly variable. The reason underlying the differential response to antibody therapy is poorly understood. The ability to predict which patients would benefit from the treatment would not only help tailor an individual's treatment plan, but it would also help avoid potentially serious adverse events, such as anaphylaxis and serum sickness, and lead to more responsible utilization of resources (given that the cost of this therapy is typically very high, often in the range of $10,000 per month). Thus, a strategy to select patients who would benefit from monoclonal antibody immunotherapy is needed.
The use of biomarkers to help guide this type of therapy has been limited to the measurement of the targeted tumor antigen itself, e.g. Her2/neu expression on breast cancer cells for trastuzumab, or CD20 expression on B-cell lymphomas for rituximab. Similarly, the expression of EGFR and the status of its downstream signaling protein, KRAS, have been predictive of potential benefits from treatment with anti-EGFR (cetuximab) in combination with chemotherapy. However, these antibody targets do not vary sufficiently to explain the heterogeneity that is seen in the clinical responses. Thus, additional ways to identify which patients may benefit from which therapy is needed. New methods for modulating an immune response against cancer cells would also be beneficial.